Реакция #41573

Уравнение реакции

pyrazine-2-carboxylic acid

hydroxybenzotriazole

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydride

4-(2-cyano-phenoxy)-5-(6-methanesulfonyl-pyridin-3-yloxy)-benzene-1,2-diamine

→

compound

5-(2-Cyano-phenoxy)-2-pyrazin-2-yl-6-(6-methanesulfonyl-pyridin-3-yloxy)-1H-benzimidazole

Растворители

dimethylformamide

ethyl acetate

ethyl acetate

Условия реакции

Обработка

1. 1
   Другоеthe reaction liquid
2. 2
   ДругоеThe reaction liquid
3. 3
   Промывкаwashed with aqueous saturated sodium bicarbonate, water and saturated saline in order
4. 4
   Сушкаdried with anhydrous sodium sulfate
5. 5
   ДругоеThe solvent was evaporated away under reduced pressure
6. 6
   workup.DISSOLUTIONthe resulting residue was dissolved in 1 ml of N-methylpyrrolidinone
7. 7
   workup.ADDITION20 mg of ytterbium trifluoromethanesulfonate was added to it
8. 8
   Другоеthe reaction liquid
9. 9
   workup.STIRRINGwas stirred at 160° C. for 2 h ours
10. 10
    ДругоеThe reaction liquid
11. 11
    Промывкаwashed with aqueous saturated sodium bicarbonate and saturated saline in order
12. 12
    Сушкаdried with anhydrous sodium sulfate
13. 13
    ДругоеThe solvent was evaporated away under reduced pressure
14. 14
    Другоеthe resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=30/1)
15. 15
    Другоеthrough partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1)

Методика

21 mg of pyrazine-2-carboxylic acid, 52 mg of hydroxybenzotriazole and 52 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide monohydride were added to a dimethylformamide (2 ml) solution of 72 mg of 4-(2-cyano-phenoxy)-5-(6-methanesulfonyl-pyridin-3-yloxy)-benzene-1,2-diamine obtained in Example 196 (step 5), and the reaction liquid was stirred at room temperature for 1 hour. The reaction liquid was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate, water and saturated saline in order, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was dissolved in 1 ml of N-methylpyrrolidinone, and 20 mg of ytterbium trifluoromethanesulfonate was added to it, and the reaction liquid was stirred at 160° C. for 2 h ours. The reaction liquid was diluted with ethyl acetate, washed with aqueous saturated sodium bicarbonate and saturated saline in order, and dried with anhydrous sodium sulfate. The solvent was evaporated away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (developing solvent: chloroform/methanol=30/1) and through partitioning thin-layer chromatography (Kieselgel™ 60F254, Art 5744 (by Merck), chloroform/methanol=10/1) to obtain the entitled compound as a brown solid.

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